Theranostic Approach Research Articles

Overview of selected completed prospective studies on PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

Theranostics in nuclear oncology combines diagnostic and therapeutic procedures using radiotracers to target tumor cells. Prostate-specific membrane antigen (PSMA) is a key target in metastatic prostate cancer, and the radioligand [177Lu]Lu-PSMA-617, which binds to PSMA, has shown promising results in treating metastatic castration-resistant prostate cancer (mCRPC), leading to its approval by the European Medicines Agency in 2022.In this narrative review, the current evidence of [177Lu]Lu-PSMA-617 in mCRPC was discussed in the context of selected studies and the joint EANM/SNMMI guidelines for Lutetium-177-labeled PSMA-targeted radioligand therapy.The use of [177Lu]Lu-PSMA-617 for post-chemotherapy mCRPC is supported by substantial evidence from the phase II TheraP and the phase III VISION trials, demonstrating its safety and efficacy. The theranostic approach identifies patients likely to benefit from [177Lu]Lu-PSMA-617, which is effective only in tumors with sufficient PSMA expression, as detected by PSMA-ligand PET/CT, which is also used for response assessment.The success of [177Lu]Lu-PSMA-617 in post-chemotherapy mCRPC patients has led to further ongoing studies evaluating its use earlier in the treatment sequence, prior to chemotherapy. To ensure beneficial treatment outcome, adequate patient selection and evaluation of imaging-based response through PSMA-ligand PET/CT is necessary. · Indications for [177Lu]Lu-PSMA-617 are based on the TheraP and VISION clinical trials.. · Adequate patient selection using PSMA-ligand PET/CT is essential for beneficial outcomes.. · Response evaluation is based on imaging, PSA levels, and the patient's clinical condition.. · Karimzadeh A, Lehnert W, Koehler D et al. Overview of selected completed prospective studies on PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer. Rofo 2025; DOI 10.1055/a-2514-4523.

Interior design model proposal for nuclear medicine imaging rooms

Innovative design approaches to prevent radiation contamination in nuclear medicine departments have been examined. Nuclear medicine departments are high-risk areas for radiation contamination due to the use of radioactive materials. The strategies employed to prevent the spread of radiation in the design of these departments have been detailed. Theranostic approaches, which utilize radiopharmaceuticals in both diagnostic and therapeutic processes, have been emphasized, and the measures aimed at minimizing radiation exposure for patients, personnel, and the public have been evaluated. The proposed design model suggests a spatial arrangement that separates the movement pathways of patients, personnel, and caregivers to minimize the risk of radiation contamination. In conclusion, it has been demonstrated that the integration of appropriate architectural design principles can significantly reduce the risk of radiation exposure in nuclear medicine departments, thereby ensuring a safe environment for both patients and healthcare professionals

GD2-targeted theranostics of neuroblastoma with [64Cu]Cu/[177Lu]Lu-hu3F8.

Neuroblastoma (NB) is a malignant embryonic tumour with poor prognosis and high mortality rate. The antigen gisialoganglioside (GD2), which is highly expressed on the surface of NB cells, is an effective target for therapy. This study aims to evaluate the GD2 expression with [64Cu]Cu-NOTA-hu3F8 positron emission tomography (PET) imaging and explore the radioimmunotherapy (RIT) effect of [177Lu]Lu-DOTA-hu3F8 in NB tumour models. The in vitro validation of the binding ability of anti-GD2 humanised monoclonal antibody (hu3F8) to GD2 was achieved via flow cytometry, cell immunofluorescence, and cell uptake test. Hu3F8 were conjugated with p-SCN-Bn-NOTA (NOTA) and p-SCN-Bn-DOTA (DOTA) for 64Cu- and 177Lu- radiolabelling. PET imaging and RIT studies were conducted using [64Cu]Cu-NOTA-hu3F8 and [177Lu]Lu-DOTA-hu3F8 in subcutaneous NB tumour models. The Institute for Medical Research-32 (IMR32) cell line exhibited a specific binding ability of hu3F8. PET imaging demonstrated a specific accumulation of [64Cu]Cu-NOTA-hu3F8 in IMR32 tumour models, with a maximum tumour uptake of 23.73 ± 2.29%ID/g (n = 3) at 72h post-injection (p.i.), outperforming other groups significantly (P < 0.001). The high dose [177Lu]Lu-DOTA-hu3F8 group (11.1MBq) showed the most potent tumour suppression, with a standardised tumour volume of about 20.47 ± 6.32% at 30 days p.i., significantly smaller than other groups (n = 5, P < 0.05). This study demonstrated that 64Cu-/177Lu- labelled hu3F8 could noninvasively evaluate the GD2 expression and effectively inhibit tumour growth in NB tumour models. The excellent therapeutic efficacy of [177Lu]Lu-DOTA-hu3F8 may be helpful for the clinical translation of this GD2-targeted theranostics approach in GD2-positive tumours.

Theranostics in Renal Cell Carcinoma-A Step Towards New Opportunities or a Dead End-A Systematic Review.

Background: Renal cell carcinoma is one of the most aggressive urogenital malignancies, with an increasing number of cases worldwide. The majority of cases are diagnosed at an advanced stage, as this form of growth is typically silent. An accurate evaluation of the extent of the disease is crucial for selecting the most appropriate treatment approach. Nuclear medicine imaging is increasingly being applied in oncological diagnostics, prompting ongoing research into renal cell carcinoma markers that could serve as a foundation for theranostic approaches in this disease. Positron emission tomography/computed tomography imaging with prostate-specific membrane antigen (PSMA) ligands has already demonstrated successful utility in diagnosis of other cancers, including prostate cancer and gliomas. Emerging evidence of high sensitivity and specificity in detecting renal cell carcinoma lesions provides a suitable foundation for its application in both the diagnosis and subsequent management of this malignancy. Methods: This systematic review synthesizes the current scientific evidence on the molecular imaging of renal cell carcinoma using PSMA ligands, emphasizing the potential future applications of this imaging marker in theranostic approaches. Results and Conclusions: Based on a systematic review of the literature, it appears that PET/CT with PSMA ligands has the potential to surpass traditional imaging techniques in diagnostic accuracy while also providing valuable prognostic information.

Amphiphilic Photoluminescent Porous Silicon Nanoparticles as Effective Agents for Ultrasound-Amplified Cancer Therapy.

This study investigates the use of photoluminescent amphiphilic porous silicon nanoparticles (αϕ-pSiNPs) as effective ultrasound (US) amplifiers for cancer sonodynamic theranostics. αϕ-pSiNPs were synthesized via a novel top-down approach involving porous silicon (pSi) films electrochemical etching, borate oxidation, and hydrophobic coating with octadecylsilane (C18), resulting in milling into nanoparticles with hydrophilic exteriors and hydrophobic interiors. These properties promote gas trapping and cavitation nucleation, significantly lowering the US cavitation threshold and resulting in selective destruction of cancer cells in the presence of nanoparticles. Efficient internalization of αϕ-pSiNPs in cell cytoplasm was demonstrated by their intrinsic photoluminescence, activated by partial oxidation of mesoporous silicon films in borate solutions, which resulted in quantum confinement of excitons in 2-5 nm Si quantum dots/wires. Combined with US exposure above the cavitation threshold, αϕ-pSiNPs caused a significant decrease in cell viability through mechanical stretching and microflows generated by oscillating microbubbles. Meanwhile, αϕ-pSiNPs exhibit high biocompatibility up to concentrations of 1 mg/mL without US activation. Their photoluminescent properties facilitate bioimaging, while their US contrast capabilities may enhance both imaging and therapy. The dual functionality of αϕ-pSiNPs supports a theranostic approach, enabling simultaneous diagnostics and treatment with a single agent. This study underscores the potential of αϕ-pSiNPs in sonodynamic therapy and bioimaging, offering a promising strategy for effective and safe anticancer therapy.

Graphene Quantum Dots‐Based Materials as an Emerging Nanoplatform in Disease Diagnosis and Therapy

AbstractGraphene quantum dots are a subclass of graphene‐based materials that exhibit unique properties due to their nanoscale size and quantum confinement effects. Discovered in the early 21st century, these zero‐dimensional carbon nanomaterials have rapidly become important in nanotechnology research due to their diverse applications. In recent years, the medical community has been greatly benefited from these materials, significantly enhancing human health and well‐being with theranostic approaches. The present review explores various applications of graphene quantum dots in diagnostic and therapeutic, unraveling their potential contributions to advancing healthcare. Furthermore, this review elucidates the synthesis methods utilized for graphene quantum dots, encompassing a range of top‐down and bottom‐up approaches. Next, the unique fundamental properties including structural, optical, and electrical that make them a potent nanomaterial for use in healthcare have been elucidated for enhanced reader comprehension. Additionally, the review explores the opportunities and challenges ahead, offering valuable insights to help the scientific community strategically expand the potential of graphene quantum dot‐based materials for advanced theranostic healthcare applications.

Preclinical Comparison of [111In]In- and [225Ac]Ac-DOTA-Trastuzumab IgG, F(ab')2 and Fab for Theranostic SPECT/CT Imaging and α-Particle Radioimmunotherapy of HER2-Positive Human Breast Cancer.

Radioimmunotherapy (RIT) with α-particle-emitting, 225Ac complexed to trastuzumab may offer an alternative treatment for patients who progress on HER2-targeted therapies. Moreover, RIT with [225Ac]Ac-DOTA-trastuzumab could be combined with SPECT/CT imaging with [111In]In-DOTA-trastuzumab in a theranostic approach. In this study, we compared DOTA-conjugated trastuzumab IgG, F(ab')2 or Fab complexed to 111In or 225Ac for SPECT/CT imaging and α-particle RIT of subcutaneous (s.c.) HER2-positive 164/8-1B/H2N.luc+ human BC tumors in NRG mice. SPECT/CT imaging and tumor and normal tissue uptake were compared in NRG or NOD-SCID mice coinjected i.v. with [111In]In-DOTA-trastuzumab IgG, F(ab')2 or Fab and [225Ac]Ac-DOTA-trastuzumab IgG, F(ab')2 or Fab. Radiation absorbed doses in the tumor and normal organs for [225Ac]Ac-DOTA-trastuzumab IgG, F(ab')2 or Fab were estimated based on the biodistribution of the [111In]In-DOTA-trastuzumab IgG, F(ab')2 or Fab. Normal tissue toxicity was assessed by hematology and blood biochemistry analyses and monitoring body weight in NRG mice injected i.v. with 2 and 4 kBq of [225Ac]Ac-DOTA-trastuzumab IgG, F(ab')2 or Fab separated by 8 d. RIT studies were performed in NRG mice with s.c. 164/8-1B/H2N.luc+ tumors injected i.v. with 2 kBq and 4 kBq of [225Ac]Ac-DOTA-trastuzumab IgG, F(ab')2 or Fab separated by 8 d or irrelevant [225Ac]Ac-DOTA-IgG1, two doses of unlabeled trastuzumab IgG or 0.9% NaCl. A tumor growth index (TGI) was plotted vs time (d) and Kaplan-Meier median survival estimated. [111In]In-DOTA-trastuzumab IgG or F(ab')2 exhibited 4.1-fold and 3.3-fold significantly greater tumor uptake at 2 d postinjection (p.i.) than Fab at 24 h p.i. However, spleen uptake at 2 d p.i. for [111In]In-DOTA-trastuzumab IgG was 3.3-fold significantly higher than F(ab')2 and 13.2-fold higher than Fab at 24 h p.i. [111In]In-DOTA-trastuzumab F(ab')2 and Fab exhibited higher kidney uptake than IgG. Tumors were imaged by SPECT/CT with [111In]In-DOTA-trastuzumab IgG and F(ab')2 but were not well-visualized with [111In]In-DOTA-trastuzumab Fab. The absorbed dose in the tumor was 2.2-fold greater for [225Ac]Ac-DOTA-trastuzumab F(ab')2 than IgG and 3.4-fold greater than Fab. Hematological toxicity was observed for [225Ac]Ac-DOTA-trastuzumab IgG but not for [225Ac]Ac-DOTA-trastuzumab F(ab')2 or Fab. No kidney or liver toxicity or decreased body weight was observed for any RIT agent. Tumor growth was significantly inhibited by [225Ac]Ac-DOTA-trastuzumab IgG, F(ab')2 or Fab but [225Ac]Ac-DOTA-trastuzumab F(ab')2 was most effective for increasing median survival (46 d vs 22 d for IgG and 29 d for Fab). We conclude that [111In]In- and [225Ac]Ac-DOTA-trastuzumab F(ab')2 exhibited superior properties for theranostic imaging and α-particle RIT of HER2-positive human BC xenografts in NRG mice.

A Single Hepatic Metastasis of Cranial Meningioma on [18F]FDG PET/CT 16 Years After Initial Surgery.

Hepatic metastases of cranial meningiomas are rare, particularly when they present as a delayed, solitary metastasis, which poses a challenge for imaging-based diagnosis. [18F]FDG PET/CT facilitates diagnosis and posttreatment restaging, whereas somatostatin receptor-targeted PET demonstrates high sensitivity and specificity in the diagnosis of meningiomas and may potentially evaluate the viability of theranostics approaches, particularly for treatment-resistant meningiomas.

Azo-linked 5-ASA-coumarin prodrug: Fluorescent tracking for colonic drug release in UC treatment

Theranostic prodrugs that enable real-time, non-invasive monitoring of drug release and biodistribution are highly desirable for optimizing therapeutic efficacy and guiding personalized medication. Herein, we report a colon-targeted theranostic prodrug system (P1) for the simultaneous delivery and tracking of 5-aminosalicylic acid (5-ASA) in the treatment of ulcerative colitis (UC). P1 comprises a fluorescent 7-amino-4-methylcoumarin (7-AMC) reporter covalently linked to 5-ASA via an azo bond, which quenches the fluorescence of 7-AMC until P1 is activated by azoreductases in the colonic microenvironment. This selective activation triggers the release of 5-ASA and the revival of 7-AMC fluorescence, enabling real-time monitoring of drug delivery. To improve the solubility and targeted delivery of P1, it was encapsulated within polymeric micelles (PM) that selectively adhere to the positively charged, inflamed colonic tissues. In vitro studies confirmed the stability, biocompatibility, and selective activation of P1 under simulated colonic conditions. Notably, in a mouse model of UC, the P1-loaded PM achieved targeted delivery of 5-ASA to the inflamed colon, resulting in effective attenuation of colitis symptoms. Importantly, the in situ activation of P1 allowed for the real-time, non-invasive visualization of drug release and biodistribution, providing valuable insights for treatment optimization. This theranostic prodrug approach offers a promising strategy for the simultaneous therapy and tracking of 5-ASA delivery in UC treatment, with the potential to facilitate personalized medication and improve therapeutic outcomes.

Norepinephrine Transporter-Targeted Cancer Theranostics-New Horizons.

In the evolving landscape of precision oncology, this review delineates the role of radiopharmaceuticals targeting the norepinephrine transporter (NET), with a particular focus on the current clinical application of 123 I-MIBG diagnostic imaging and 131 I-MIBG therapeutics, in particular for pheochromocytoma, neuroblastoma, or paraganglioma. We will also highlight recently introduced 18 F-labeled NET targeting imaging radiotracers, which would offer unparalleled resolution, enhanced tumor localization, and staging properties. Complementing these novel second-generation PET agents in a theranostic approach, astatine-211 meta-astatobenzylguanidine ( 211 At-MABG) would leverage the advantages of alpha-particles to selectively target and eradicate NET-expressing tumor cells with minimal off-target effects.

NIMG-34. CXCR4-TARGETED PET IMAGING OF CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOMA USING [68GA]GA-PENTIXAFOR

Abstract BACKGROUND Initial results suggest that PET imaging of the chemokine receptor CXCR4 is of considerable interest for differential diagnosis and theranostic approaches. Here, we summarized findings of CXCR4 PET imaging in an institutional series of lymphoma of the central nervous system (CNSL) and glioma. METHODS Twenty-three patients with CNSL and 16 patients with glioma (IDH-wildtype, n=9) underwent PET imaging using the CXCR4-directed tracer [68Ga]Ga-Pentixafor. In 18 patients, serial PET imaging was performed (range, 2-14 scans), resulting in a total of 104 PET scans. For evaluation, PET scans were classified as [68Ga]Ga-Pentixafor-positive and -negative visually, and the maximum standardized uptake value (SUVmax) was obtained from [68Ga]Ga-Pentixafor-PET. RESULTS Twenty-four of all 39 patients (62%) had at least one [68Ga]Ga-Pentixafor-positive PET (CNSL, 57%; glioma, 69%). [68Ga]Ga-Pentixafor-positive PET scans were more common in patients with IDH-wildtype gliomas (89%) than in IDH-mutant gliomas (43%). In patients with [68Ga]Ga-Pentixafor-positive PET, the average SUVmax was 6.4±4.0 in CNSL, and 3.4±1.0 in gliomas (P=0.155). Besides visualization of tumors, [68Ga]Ga-Pentixafor uptake was observed in two patients with radionecrosis. In four CNSL patients who had undergone methotrexate/cytarabine-based first-line therapy, serial PET revealed a significant reduction of SUVmax after chemotherapy completion (average decrease of SUVmax from 4.5±3.8 to 0.6±0.7; P=0.044). In three of those four patients, tumor progression has not been reached (range of time after the follow-up PET, 4-55 months); one patient deceased 44 months after the follow-up PET. In contrast, another patient with an increase in SUVmax from 6.9 to 11.0 after first-line treatment died one month after the follow-up PET. DISCUSSION [68Ga]Ga-Pentixafor PET seems to be of value for non-invasively visualizing and quantifying CXCR4 receptor binding. In CNSL, changes in [68Ga]Ga-Pentixafor uptake following therapy may indicate potential for response assessment. CXCR4-targeting radioligand therapies might be more promising in CNSL than in glioma.

PHARMACEUTICAL NANOCRYSTALS: AN EXTENSIVE OVERVIEW

In pharmaceutical development, pharmaceutical nanocrystals sized between 10 and 1000 nanometers have been found to hold promise in improving drug solubility. Since they comprise only the active pharmaceutical ingredient, nanocrystals have dramatically increased surface area-to-volume ratios, ensuring improved in vitro dissolution and solubility profiles. In view of their strengths and limitations, different production strategies have been reviewed: methods of size reduction such as wet milling and high-pressure homogenization; the bottom-up approaches of controlled precipitation and supercritical fluid technology; and efficient ways to stabilize nanocrystal formulations aided by excipients like surfactants and polymers. Techniques used in this characterization of nanocrystals include size analysis, surface-charge measurement, and assessment of crystalline structure. The routes of administration, such as oral, injectable, inhaled, and topical application, are reviewed alongside commercially successful products and clinical trials. This work reviews dynamic regulatory scenarios and current challenges of large-scale production, long-term stability, and nanotoxicity evaluation. In addition, it addresses the emerging trends in nanocrystal technology in the field of personalized medicine, targeted drug delivery, and theranostic approaches associated with how nanocrystals can help optimize the outcome of a patient in drug delivery systems.

MicroRNA-219 in the central nervous system: a potential theranostic approach

Despite the recent therapeutic advances in neurological disorders, curative therapy remains a serious challenge in many cases. Even though recent years have witnessed the development of gene therapy from among the different therapeutic approaches affecting pathophysiological mechanisms, intriguing aspects exist regarding the effectiveness, safety, and mechanism of action of gene therapies. Micro ribonucleic acid (microRNA-miRNA), as a fundamental gene regulator, regulates messenger ribonucleic acid (mRNA) by directly binding through the 3′-untranslated region (3′-UTR). MicroRNA-219 is a specific brain-enriched miRNA associated with neurodevelopmental disorders that play crucial roles in the differentiation of oligodendrocyte progenitorcells, promotion of oligodendrocyte maturation, remyelination, and cognitive functions to the extent that it can be considered a potential therapeutic option for demyelination in multiple sclerosis and spinal cord injury and reverse chronic inflammation pains. Additionally, miR-219 regulates the circadian clock, influencing the duration of the circadian clock period. This regulation can impact mood stability and is associated with phase fluctuations in bipolar patients. Furthermore, miR-219 also plays a role in modulating tau toxicity, which is relevant to the pathophysiology of Alzheimer’s disease and schizophrenia. Finally, it reportedly has protective effects against seizures and Parkinson’s disease, as well as neoplasms, by inhibiting proliferation, suppressing invasion, and inducing cell death in tumor cells. Exploring the miR-219 molecular pathways and their therapeutic effects on central nervous system disorders and the mechanisms involved, the present review study aims to illustrate how this information may change the future of gene therapy.

Potential of PSMA for breast cancer in nuclear medicine: digital quantitative immunohistochemical analysis and implications for a theranostic approach

BackgroundFurther research is still needed to fully understand the potential of prostate-specific membrane antigen (PSMA) in breast cancer (BC) and to develop and optimize targeted therapies and imaging modalities. The objective of this study was to present a comprehensive analysis of immunohistochemistry data on PSMA staining in BC and to discuss its potential value in a theranostic approach.MethodsFifty-eight male and female patients were randomly selected from a retrospective database of patients who underwent surgery for breast cancer between January 2012 and December 2017 and for whom a specimen is available in our tumour library. Immunodetection of PSMA and CD31 was performed on serial slides. The digitized slides were reviewed and analysed by an experienced pathologist. Additionally, the corresponding TIFF images were processed to calculate the percentage of positive neovessels.ResultsEighteen patients (31.6%) had no expression, 29 (50.9%) had PSMA neovascular expression scored as “1”, and 10 (17.5%) had neovascular expression scored as “2”. Digital immunohistochemistry analysis for this last specific group of patients showed a median proportion of positive neovessels equal to 5% (range: 3–19). A multivariable logistic regression demonstrated that the odds of PSMA positivity were 4.55 times higher in non-luminal tumours and decreased by a factor of 0.12 in lobular subtypes. There was no association between sex or the presence of a germline BRCA1/2 mutation and PSMA expression in tumours.ConclusionsOur study highlights generally low neovascular expression of PSMA in specific histopathological subtypes of breast cancer, which will likely hamper the development of an adequate theranostic strategy.Trial registrationThe procedure has been retrospectively registered to the French National Institute for Health Data (N° F20220615153900).

Li-Fraumeni Syndrome in Breast Cancer: Development of Theranostic Probes on Variation of P53

Li-Fraumeni Syndrome (LFS) is a hereditary condition characterized by a high predisposition to various cancers due to mutations in the p53 protein. Effectively targeting and treating this syndrome requires early detection and personalized treatment according to one’s specific nucleotide sequence. With the use of various forms of theranostics, LFS can be treated, increasing life expectancy; however, there is no absolute cure that could immediately end this syndrome. This paper delves into three different theranostic approaches: Gendicine (rAd-p53), Phesgo, and gold nanoshell poly(D, L-lactic-co-glycolic acid) nanoparticles (PLGA NPs). While each approach has limitations, PLGA nanoparticles exhibit advantages that outweigh their drawbacks, making it an attractive solution. This proposal will describe improvements to PLGA nanoparticles, which are a promising area of research for the development of new LFS treatments.

Precision Population Cancer Medicine in Brain Tumors: A Potential Roadmap to Improve Outcomes and Strategize the Steps to Bring Interdisciplinary Interventions.

Brain tumors, a significant health burden,rank as the second leading cause of cancer among adolescents and young adults and the eighth most common cancer in older adults. Despitetreatment advances, outcomesfor many brain tumor types,especiallyglioblastoma multiforme (GBM), remain poor. Precision population cancer medicine (PPCM) offerspromising avenues for improving outcomes in brain tumor management.This comprehensive reviewdelves intothe current landscape of brain tumor diagnosis and treatment,with a primary focus onthe potential of PPCM toenhancecare. The reviewexploresseveral key areas where PPCM approaches show promise. In genetics and molecular biology, the genetic heterogeneity of brain tumors poses challengesandopportunities for targeted therapies. Understanding genetic patterns canguidetreatment strategies and improve prognostication. Epigenetic modificationsarecrucialin brain tumor development and progression. Deoxyribonucleic acid(DNA) methylation patterns, particularly of theO6-methylguanine-DNA methyltransferase (MGMT) gene promoter, serve asessentialbiomarkers for treatment response and prognosis in GBM. Targeting epigenetic mechanisms could lead to novel therapeutic approaches. Non-invasive liquid biopsy techniques show potential for diagnosis, monitoring, and prognostication in brain tumors. Analysis of circulating tumor DNA and microRNAs may provide valuable information about tumor characteristics and treatment response. Advanced imaging techniques, including radiomics and radiogenomics, combined with artificial intelligence (AI) algorithms, are enhancing tumor detection, characterization, and treatment planning. These technologies can contribute to more personalized treatment approaches.In addition, emergingnanotherapeutic platforms, which involve the use of nanoparticles to deliver drugs directly to tumors,and theranostic approaches, which combine therapy and diagnostics in a single platform,offer new possibilities for targeted drug delivery and real-time treatment monitoring in brain tumors. The review also addresses socioeconomic and demographic factors influencing brain tumor incidence and outcomes. It highlightsthe starkdisparities in care access and survival rates among different racial and ethnic groups, emphasizing theurgentneed for PPCM strategies to address these inequities. Challenges in implementing PPCM for brain tumors include the blood-brain barrier, which limits drug delivery, and the need for more extensive clinical trials to validate new approaches. The authors stress the importance of interdisciplinary collaboration and data sharing to advance the field, making the audience feel united and part of a larger team. While PPCM holds great promise, the review emphasizes that it should complement, not replace, population-level interventions and standard-of-care treatments. The authors advocate for a balanced approach that leverages cutting-edge personalized strategies while ensuring broad access to effective treatments. In conclusion, PPCM represents a powerful tool in the fight against brain tumors, offering the potential for more targeted, effective, and less toxic treatments. However, realizing its full potential will require ongoing research, clinical validation, and policy interactionsto address disparities in care access.

18F]FDG PET for mapping the cerebral glucose metabolic characteristics of drug-sensitive and drug-resistant epilepsy in pediatric patients.

This study aimed to investigate [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) mapping for cerebral glucose metabolism in drug-sensitive and drug-resistant pediatric epilepsy patients. This retrospective study enrolled 40 patients and 25 controls. Patients were categorized into drug-sensitive epilepsy (n = 22) and drug-resistant epilepsy (n = 18) according to the seizure frequency at follow-up. All patients underwent two [18F]FDG PET scans separated by a minimum of one year. Absolute asymmetry index (|AI|) was calculated for assessing metabolic differences and changes in epileptic foci. Statistical Parametric Mapping (SPM) was utilized to reveal voxel-wise metabolic characteristics and alterations throughout the brain. Network analysis based on graph theory was used to investigate network-level differences between the two patient groups. The drug-sensitive group showed a lower |AI| at both baseline (P = 0.038) and follow-up (P = 0.003) PET scans than the drug-resistant group. |AI| decreased in the drug-sensitive group and increased in the drug-resistant group across scans, but these trends were not statistically significant (P = 0.240 and P = 0.450, respectively). Both groups exhibited hypometabolism at baseline. The drug-sensitive group showed less hypometabolic brain regions than the drug-resistant group. The drug-sensitive maintained stable level of hypometabolism between the two scans, whereas the drug-resistant group showed an increasing hypometabolism. Network analysis demonstrated that the drug-sensitive group had a higher global efficiency, average degree, and clustering, along with a shorter characteristic path length compared to the drug-resistant group. For the first time, this study revealed in vivo cerebral glucose metabolic pattern of nonsurgical pediatric epilepsy patients treated by antiepileptic drugs. Especially, drug-resistant epilepsy patients represented significantly extensive and progressive hypometabolism with inefficient brain network connectivity compared with drug-sensitive epilepsy. [18F]FDG PET imaging may be a potential visual approach for theranostics of epilepsy patients.

Médecine nucléaire et cancers de la thyroïde en 2024 : iode 131, TEP et nouvelles approches théranostiques

NUCLEAR MEDICINE AND THYROID CANCERS IN 2024: IODINE 131, PET AND NEW THERANOSTIC APPROACHES: Nuclear medicine has long been a mainstay in the management of thyroid cancers. In patients with differentiated thyroid cancer (DTC), the most common histotype, radioiodine (RAI, 131I) has been for years a cornerstone for the treatment of RAI-avid metastases. Post-therapeutic 131I scintigraphy helps guide these treatments and contributes to the definition of refractory cancers. In these refractory patients, who represent fewer than 5% of CTDs, 18FDG PET plays a central diagnostic and prognostic role. From a therapeutic perspective, RAI uptake can be re-induced in some of these patients with the BRAF mutation by using redifferentiation protocols. In anaplastic thyroid cancer (A TC) that is rare, aggressive and undifferentiated, 18FDG PET remains the metabolic imaging of choice. In medullary thyroid cancer (MTC), PET imaging is mainly based on the use of 18F-DOPA, even if 18FDG also provides prognostic data and 68Ga-DOTATOC could allow a theranostic approach. Other radiopharmaceuticals offering new theranostic avenues in thyroid cancers are also discussed, such as prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP). After decades of a "one-size fits all" approach in thyroid cancer management, molecular imaging is paving the way towards personalized medicine.

Engineering AIEgens-Tethered Gold Nanoparticles with Enzymatic Dual Self-Assembly for Amplified Cancer-Specific Phototheranostics.

Accurate imaging and precise treatment are critical to controlling the progression of pancreatic cancer. However, current approaches for pancreatic cancer theranostics suffer from limitations in tumor specificity and invasive surgery. Herein, a pancreatic cancer-specific phototheranostic modulator (AuHQ) dominated by aggregation-induced emission (AIE) luminogens-tethered gold nanoparticles is meticulously designed to facilitate prominent fluorescence-photoacoustic bimodal imaging-guided photothermal immunotherapy. Once reaching the pancreatic tumor microenvironment (TME), the peptide Ala-Gly-Phe-Ser-Leu-Pro-Ala-Gly-Cys (AGFSLPAGC) linkage within AuHQ can be specifically cleaved by the overexpressed enzyme Cathepsin E (CTSE), triggering the dual self-assembly of AuNPs and AIE luminogens. The aggregation of AuNPs mediated by enzymatic cleavage results in potentiated photothermal therapy (PTT) under near-infrared (NIR) laser irradiation, induced immunogenic cell death (ICD), and enhanced photoacoustic imaging. Simultaneously, AIE luminogen aggregates formed by hydrophobic interaction can generate AIE fluorescence, enabling real-time and specific fluorescence imaging of pancreatic cancer. Furthermore, coadministration of an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with AuHQ can address the limitations of PTT efficacy imposed by the immunosuppressive TME and leverage the synergistic potential to activate systemic antitumor immunity. Thus, this well-designed phototheranostic modulator AuHQ facilitates the intelligent enzymatic dual self-assembly of imaging and therapeutic agents, providing an efficient and precise approach for pancreatic cancer theranostics.

Theranostic Approaches for Gastric Cancer: An Overview of In Vitro and In Vivo Investigations

Gastric cancer (GC) is the second most common cause of cancer-related death worldwide and a serious public health concern. This high death rate is mostly caused by late-stage diagnoses, which lead to poor treatment outcomes. Radiation immunotherapy and targeted therapies are becoming increasingly popular in GC treatment, in addition to surgery and systemic chemotherapy. In this review, we have focused on both in vitro and in vivo research, which presents a summary of recent developments in targeted therapies for gastric cancer. We explore targeted therapy approaches, including integrin receptors, HER2, Claudin 18, and glutathione-responsive systems. For instance, therapies targeting the integrin receptors such as the αvβ3 and αvβ5 integrins have shown promise in enhancing diagnostic precision and treatment efficacy. Furthermore, nanotechnology provides novel approaches to targeted drug delivery and imaging. These include glutathione-responsive nanoplatforms and cyclic RGD peptide-conjugated nanoparticles. These novel strategies seek to reduce systemic toxicity while increasing specificity and efficacy. To sum up, the review addresses the significance of personalized medicine and advancements in gastric cancer-targeted therapies. It explores potential methods for enhancing gastric cancer prognosis and treatment in the future.